January 2007

Fig.4

Diagnosis: Incontinentia Pigmenti

Histopathology: Acanthosis, marked spongiosis, intracorneal eosinophilic pustules, dyskeratotic keratinocytes (Figure 4)

Discussion: Incontinentia Pigmenti is a X-linked dominant genodermatosis. It is characterized by 4 cutaneous stages: vesicular, verrucous, hyperpigmented, and atrophic. A majority of patients display extra-cutaneous manifestations. These include neurologic (seizures), ophthalmologic (defects in retinal vasculature), and dental (absent or peg-shaped teeth) findings.
The genetic defect responsible for IP resides in the NEMO gene (NF-kB essential modulator). Mutations in NEMO result in male lethality although there have been case reports of IP in patients with Klinefelter (XXY) and possibly with hypomorphic alleles of NEMO. In females X-inactivation results in mosaicism for NEMO. That is, clones of epidermal cells either express the mutant or the wild-type NEMO allele based on random X-inactivation. Those clones that have the mutant NEMO give rise to the cutaneous findings of the disease.
Targeted disruption of NEMO in mice results in a strikingly similar phenotype to IP. This includes male lethality, stereotyped cutaneous eruption involving vesicles evolving into pigmentation stripes.

Follow-up: Our patient had a short inpatient stay before being discharged to home. The patient was referred to ophthalmology and neurology. Several months later eye exam revealed retinal neovascularization which was successfully treated with laser ablation. The retinal defects in IP are felt to result from initial ischemic infarcts/occlusion giving rise to retinal neovascularization, hemorrhages, and detachments.

References:
Aradhya et al. 2001. A recurrent deletion in the ubiquitously expressed NEMO (IKK) gene accounts for the vast majority of incontinentia pigmenti mutations. Human Molecular Genetics 10(19): 2171-2179.
Berlin, Paller, and Chan. 2002. Incontinentia pigmenti: A review and update on the molecular basis of pathophysiology. JAAD 47(2): 169-187.
Goldberg. 2004. The skin is not the predominant problem in Incontinentia Pigmenti. Arch Dermatol. 140:758-750.
Schmidt-Supprian et al. 2000. NEMO/IKK-Deficient Mice Model Incontinentia Pigmenti. Molecular Cell 5: 981-992

This case is presented by Drs. Omar Jassim, Laurence Cheung, and Susan Bayliss.